[摘要] 免疫检查点阻断（ICB）治疗，尤其是PD-1/PD-L1 和CTLA-4 阻断性抗体，在晚期恶性肿瘤治疗上取得了令人瞩目的成绩，美国FDA已经批准该疗法应用于包括黑色素瘤、肾癌、小细胞肺癌以及所有微卫星不稳定的晚期肿瘤患者的临床治疗。然而，随着近年来临床前试验和临床实践的不断拓展和深入，该疗法的局限性也逐步显现。例如即使在反应性良好的肿瘤类型中，临床治疗的有效率仅维持在20%~30%，甚至还出现了一些治疗后促进肿瘤的进展和转移的病例。因此，是什么因素决定或者限制了ICB疗法的有效性？什么类型的肿瘤患者才能从中受益？哪个（或哪些）生物标志物可用于受益患者的筛选、治疗效果的评价及预后的判断？上述问题的阐明对该领域的研究将产生极大的推动作用。本文从ICB抗肿瘤机制出发，重点讨论制约ICB疗效的关键因素以及当前与ICB联合抗肿瘤研究的进展，旨在梳理哪些生物标志物可以用于ICB治疗的伴随诊断以及未来ICB联合治疗的应用前景，以期为ICB抗肿瘤的精准医学研究提供参考。

[Abstract] Immune-checkpoint blockade (ICB) therapy, especially PD-1/PD-L1 and CTLA-4 blocking antibodies, has achieved surprising curative effects in advanced cancer patients. The US FDA has approved ICB treatment for melanoma, small cell lung carcinoma,kidney carcinoma, and all solid tumors with microsatellite instability. However, with the expansion and deepening of pre-clinical trials and clinical applications in recent years, the limitations of ICB immunotherapy have gradually emerged. For example, even in well-responded tumor types, the effective rate of ICB therapy is only 20%-30%, and there are even cases with tumor progression and metastasis.Therefore, what factors determine or limit the effectiveness of ICB therapy? What kind of patients can benefit from it? Which biomarkers can be used for screening beneficiary patients, evaluating therapeutic outcomes and prognosis? The clarification of above issues will greatly promote the research in this field. In this review, based on the anti-tumor mechanism of ICB, we discuss the recent progress in this field, with an emphasis on the key factors restricting the efficacy of ICB treatment and the current combined therapeutic strategies with ICB, aiming to reveal which biomarkers can be used in the concomitant diagnosis of ICB therapy and the future application perspective of ICB combined therapies, to provide reference for the precision medicine of ICB anti-tumor therapy.

国家自然科学基金资助项目（No. 31770966，31570869）